Lung disease is the third most frequent cause of death in this country, claiming -360,000 Americans annually. Tragically, an additional 25 million live with chronic lung diseases including asthma, emphysema, cancer and cystic fibrosis. Unfortunately, the number of individuals with lung disease is increasing at an alarming rate, thus, a better understanding of the etiology of lung disease and new therapeutics to treat lung disease are required. Based on the success of the initial 5-year COBRE award, the ultimate goals of this COBRE renewal application are: 1) to recruit additional faculty investigators who are engaged in lung biology research; 2) to continue to mentor existing junior faculty in the program; 3) to increase extramural funding for COBRE investigators in lung biology; and 4) to establish a Center for Lung Biology that will be nationally recognized and free standing in five years. With the foundation of a developing Lung Biology Program, which has been substantially enhanced by initial COBRE support, this proposal takes advantage of a highly interactive core of existing, collaborative faculty at Dartmouth Medical School (DMS), Dartmouth Hitchcock Medical Center (DHMC), the Thayer School of Engineering at Dartmouth and Keene State College. With this solid base of investigators, continuation of COBRE support will provide the resources to develop the Program and facilitate inter-disciplinary lung biology research in five ways: 1) recruitment of four new tenure-track faculty; 2) mentored development of four promising junior investigators who are Project Leaders of the Research Projects, which are multi-disciplinary,' characteristic of a center, and are intertwined by the common theme of lung disease; 3) mentored development of investigators previously supported by COBRE; 4) enhanced research infrastructure by expansion of the Proteomic Core, and the full integration of the Core with shared services of other DMS and DHMC Cores including Bioinformatics and Biostatistics, and; 5) synergistic scientific collaboration through the four COBRE Research Projects, associated Cores, and other basic and translational infrastructure and programs at DMS/DHMC. Together with institutional commitment by DMS, there is confidence that the existing cadre of investigators, already expanded and matured by the COBRE mechanism, can be further developed to establish a Center for Lung Biology that is grounded in basic research and embraces a translational approach to promote bidirectional bench-to-bedside research.